Developments in recombinant DNA technology have enabled the cloning in bacteria of the natural coding sequence of a variety of genes. [See Seeburg, P H., Shine, J., Martial, J. A., Baxter, J. D. and Goodman, H. M., Nature 270, 486-494 (1977) and Shine, J., Seeburg, P. H., Martial, J. A , Baxter, J. D. and Goodman, H. M., Nature 270, 494-499 (1977); Keshet, E., Rosner, A., Bernstein, Y., Gorecki, M. and Aviv, H., Nucleic Acids Res 9, 19 (1981); Miller, W. L., Martial, J. A and Baxter, J. D., J. Biol. Chem. 255, 7521-7524 (1980)]. Recently, recombinant DNA techniques have been described in which a foreign protein is cloned and expressed in yeast. Evidence for foreign gene expression in yeast came from studies on the in vivo transcription of a rabbit globin gene introduced into Saccharomyces cerevisiae on a yeast plasmid vector. [See Beggs, J. D , van den Berg, J., van Obyen, A , and Weissmann, C., Nature 283, 835-840 (1980).]
In an attempt to maximize expression of foreign genes in yeast, their 5'-promoter region, translation start and signal peptide sequences were replaced with similar regions from the yeast genome. With bovine growth hormone, these regions were replaced with those from the yeast alcohol dehydrogenase (ADH1) gene. Full length, biologically active bovine growth hormone molecules were produced in yeast. [See Hitzeman, R. A., Hagie, F. E., Levine, H. L., Goeddel, D. V., Ammerer, G., and Hall, B. D., Nature 295, 717-722 (1981).] Other promoters were employed but demonstrated much less gene expression. The ability of having a single strong promoter is highly useful to permit the attainment of substantial levels of expression for a variety of genes in yeast.
It has now been discovered that promoters for the GAL1 galactokinase gene are such a promoters. In addition, these promoters are under glucose repression. Thus, it becomes practical to clone any one of a variety of genes including bovine growth hormone, interferon, pre-prorennin and prorennin in yeast with expression maximized by direction of a yeast GAL1 promoter.